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J Clin Oncol. 2016 Jul 20;34(21):2460-7. doi: 10.1200/JCO.2015.64.8931. Epub 2016 May 2.

Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study.

Author information

1
Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium. rnanda@medicine.bsd.uchicago.edu.
2
Rita Nanda, University of Chicago, Chicago, IL; Laura Q.M. Chow, University of Washington, Seattle, WA; E. Claire Dees, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC; Raanan Berger, Sheba Medical Center, Tel Hashomer; Ravit Geva, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Shilpa Gupta, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Lajos Pusztai, Yale University School of Medicine, New Haven, CT; Kumudu Pathiraja, Gursel Aktan, Jonathan D. Cheng, and Vassiliki Karantza, Merck & Co., Kenilworth, NJ; and Laurence Buisseret, Université Libre de Bruxelles, Bruxelles, Belgium.

Abstract

PURPOSE:

Immune checkpoint inhibition has been demonstrated to be an effective anticancer strategy. Several lines of evidence support the study of immunotherapy in triple-negative breast cancer (TNBC). We assessed the safety and antitumor activity of the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab in patients with advanced TNBC.

METHODS:

KEYNOTE-012 (ClinicalTrials.gov identifier: NCT01848834) was a multicenter, nonrandomized phase Ib trial of single-agent pembrolizumab given intravenously at 10 mg/kg every 2 weeks to patients with advanced PD-L1-positive (expression in stroma or ≥ 1% of tumor cells by immunohistochemistry) TNBC, gastric cancer, urothelial cancer, and head and neck cancer. This report focuses on the TNBC cohort.

RESULTS:

Among 111 patients with TNBC whose tumor samples were screened for PD-L1 expression, 58.6% had PD-L1-positive tumors. Thirty-two women (median age, 50.5 years; range, 29 to 72 years) were enrolled and assessed for safety and antitumor activity. The median number of doses administered was five (range, 1 to 36 doses). Common toxicities were mild and similar to those observed in other tumor cohorts (eg, arthralgia, fatigue, myalgia, and nausea), and included five (15.6%) patients with grade ≥ 3 toxicity and one treatment-related death. Among the 27 patients who were evaluable for antitumor activity, the overall response rate was 18.5%, the median time to response was 17.9 weeks (range, 7.3 to 32.4 weeks), and the median duration of response was not yet reached (range, 15.0 to ≥ 47.3 weeks).

CONCLUSION:

This phase Ib study describes preliminary evidence of clinical activity and a potentially acceptable safety profile of pembrolizumab given every 2 weeks to patients with heavily pretreated, advanced TNBC. A single-agent phase II study examining a 200-mg dose given once every 3 weeks (ClinicalTrials.gov identifier: NCT02447003) is ongoing.

PMID:
27138582
DOI:
10.1200/JCO.2015.64.8931
[Indexed for MEDLINE]

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